Consumption of pasteurized human lysozyme transgenic goats’ milk alters serum metabolite profile in young pigs

Nutrition, bacterial composition of the gastrointestinal tract, and general health status can all influence the metabolic profile of an organism. We previously demonstrated that feeding pasteurized transgenic goats’ milk expressing human lysozyme (hLZ) can positively impact intestinal morphology and modulate intestinal microbiota composition in young pigs. The objective of this study was to further examine the effect of consuming hLZ-containing milk on young pigs by profiling serum metabolites. Pigs were placed into two groups and fed a diet of solid food and either control (non-transgenic) goats’ milk or milk from hLZ-transgenic goats for 6 weeks. Serum samples were collected at the end of the feeding period and global metabolite profiling was performed. For a total of 225 metabolites (160 known, 65 unknown) semi-quantitative data was obtained. Levels of 18 known and 4 unknown metabolites differed significantly between the two groups with the direction of change in 13 of the 18 known metabolites being almost entirely congruent with improved health status, particularly in terms of the gastrointestinal tract health and immune response, with the effects of the other five being neutral or unknown. These results further support our hypothesis that consumption of hLZ-containing milk is beneficial to health

Diagnostic indicators of superimposed preeclampsia in women with CKD

Introduction: Diagnosis of superimposed preeclampsia in women with chronic kidney disease (CKD) is complicated by the presence of hypertension and proteinuria due to renal disease. The aims of this study were to determine mechanistic links between superimposed preeclampsia and renin-angiotensin system activation, endothelial pathology, complement dysfunction, and tubular injury, and to explore the role of diagnostic indicators of superimposed preeclampsia. Methods: Plasma and urinary biomarkers derived from the renin-angiotensin system (active renin, angiotensinogen), endothelial glycocalyx (hyaluronan, intercellular adhesion molecule, vascular cell adhesion molecule [VCAM], P-selectin, E-selectin), complement activation (C3a, C5a, complement factor H, C5b-9), and tubular injury (kidney injury molecule-1, urinary lipocalin-2) were quantified in 60 pregnant women with CKD including 15 women at the time of superimposed preeclampsia diagnosis and 45 women who did not develop superimposed preeclampsia, 18 women with preeclampsia, and 20 normal pregnancies. Correlation with placental growth factor was assessed. Results: Plasma concentrations of hyaluronan (67.5 ng/ml vs. 27.5 ng/ml, P ¼ 0.0017, receiver operating characteristic area 0.80) and VCAM (1132 ng/ml vs. 659 ng/ml, P < 0.0001, receiver operating characteristic area 0.86) distinguished women with CKD and superimposed preeclampsia from those without superimposed preeclampsia, and correlated with placental growth factor concentration. The diagnostic discrimination of markers of the renin-angiotensin system was reduced by adjustment for chronic hypertension, antihypertensive drug use, and black ethnicity. Other markers offered limited or no diagnostic discrimination for superimposed preeclampsia. Conclusion: This study suggests that endothelial dysfunction contributes to the pathophysiology of superimposed preeclampsia and a diagnostic role for plasma hyaluronan and VCAM is hypothesized

Influence of maternal pre-pregnancy body composition and diet during early-mid pregnancy on cardiovascular function and nephron number in juvenile sheep.

The prenatal diet can program an individual's cardiovascular system towards later higher resting blood pressure and kidney dysfunction, but the extent to which these programmed responses are directly determined by the timing of maternal nutritional manipulation is unknown. In the present study we examined whether maternal nutrient restriction targeted over the period of maximal placental growth, i.e. days 28-80 of gestation, resulted in altered blood pressure or kidney development in the juvenile offspring. This was undertaken in 6-month-old sheep born to mothers fed control (100-150 % of the recommended metabolisable energy (ME) intake for that stage of gestation) or nutrient-restricted (NR; 50 % ME; n 6) diets between days 28 and 80 of gestation. Controls were additionally grouped according to normal (>3, n 7) or low body condition score (LBCS; <2, n 6), thereby enabling us to examine the effect of maternal body composition on later cardiovascular function. From day 80 to term (approximately 147 d) all sheep were fed to 100 % ME. Offspring were weaned at 12 weeks and pasture-reared until 6 months of age when cardiovascular function was determined. Both LBCS and NR sheep tended to have lower resting systolic (control, 85 (se 2); LBCS, 77 (se 3); NR, 77 (se 3) mmHg) and diastolic blood pressure relative to controls. Total nephron count was markedly lower in both LBCS and NR relative to controls (LBCS, 59 (se 6); NR, 56 (se 12) %). Our data suggest that maternal body composition around conception is as important as the level of nutrient intake during early pregnancy in programming later cardiovascular health

Adenosine receptors in gestational diabetes mellitus and maternal obesity in pregnancy

Regulation of blood flow depends on the systemic and local release of vasoactive molecules including the endogenous nucleoside adenosine. Vasodilation caused by adenosine results from the activation of adenosine receptors (ARs) at the vascular endothelium and smooth muscle. Adenosine receptors are four subtypes, i.e. AAR, AAR, AAR and AAR, of which AAR and AAR activation in the endothelium lead to increased generation of nitric oxide and relaxation of the underlying smooth muscle cell layer. Adenosine also causes vasoconstriction via a mechanism involving AAR activation by increasing the release of vasoconstrictors. Adenosine increases the sensitivity of vascular tissues from diseases coursing with insulin resistance, including gestational diabetes mellitus (GDM) and obesity. ARs also play a role in obesity since they modulate D-glucose homeostasis, inflammation and adipogenesis. Agonists and/or antagonists of high selectivity for ARs may result in reversing the obesity state since normalises lipolysis and insulin sensitivity. A considerable fraction of pregnant women with GDM show with pregestational obesity and/or supraphysiological gestational weight gain. These conditions associated with reduced vascular responsiveness to adenosine and insulin. However, it is unclear whether GDM plus obesity in pregnancy could worsen these alterations in the foetoplacental vascular function. This chapter summarises available findings that address the potential involvement of ARs to modulate human foetoplacental vasculature in GDM and obesity in pregnancy